Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
  • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
  • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
  • C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D263/36—One oxygen atom
  • C07D263/42—One oxygen atom attached in position 5

Definitions

• the invention is concerned with a process for the production of N-acetyl-DL-penicillamine from DL-valine by converting the valine into 2-methyl-4-isopropylidene-2-oxazolin-5-one using chloroacetyl chloride and converting the 2-methyl-4-isopropylidene-2-oxazolin-5-one into the N-acetyl-DL-penicillamine.
• N-acetyl-DL-penicillamine serves as a starting material for the recovery of DL-penicillamine.
• the valine can be introduced directly into the chloroacetyl chloride.
• organic solvents there are suitably used materials which are inert to the reactants under the reaction conditions.
• aliphatic and aromatic hydrocarbons e.g., gasoline having boiling points between 80° and 200°C., n-heptane, n-octane, n-decane, 2,2,4-trimethylpentane, undecane, dodecane, n-hexadecane and other alkanes, cyclohexane, benzene, toluene, xylene, halo substituted hydrocarbons, especially chloro substituted hydrocarbons such as haloalkanes, e.g., carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethane, 1,1,1-trichloroethane, 1,1,2-trichloroethane, chloropropane, chlorobenzene, o-dichlorobenzene, or ethers, e.g., alkyl ethers such as diisopropyl ether
• chloroacetyl chloride it is suitable to use at least equivalent amounts of chloroacetyl chloride to the valine, i.e., mole for mole.
• the molar ratio of chloroacetyl chloride can be as large as one wishes, i.e., there is no upper limit. In a given case the higher the water content of the materials the more chloroacetyl chloride is necessary. In adding water free materials it can be advantageous not to exceed a molar ratio of chloroacetyl chloride to valine of 4 to 1.
• the reaction takes place in a suitable manner at temperatures between about 50° and 150°C., preferably between 70° and 120°C.
• the pressure can range widely and is not critical. However, it is recommended in order to use simple apparatus to employ normal pressure, or if necessary moderately reduced or elevated pressures.
• the temperature and pressure in a given case to a certain extent are adjusted according to the type of solvent and the molar ratio of chloroacetyl chloride to valine.
• N-acetyl-DL-penicillamine can take place in known manner, for example, according to a process set forth in the Chemistry of Penicilline, Princeton University Press, 1949, especially pages 464 to 466. The entire disclosure of The Chemistry of Penicilline pages 464 to 466 is hereby incorporated by reference.
• an organic base especially a tertiary amine or base such as triethylamine, tributyl amine or N-methyl morpholine in an inert solvent, especially in a hydrocarbon (such as those set forth above, for example) or an ether (such as those set forth above, for example), or an alcohol, e.g., methyl alcohol, ethyl alcohol, isopropyl alcohol, propyl alcohol or butyl alcohol or an ester, e.g., methyl acetate, ethyl acetate, propyl acetate, methyl propionate or ethyl butyrate.
• an organic base especially a tertiary amine or base such as triethylamine, tributyl amine or N-methyl morpholine in an inert solvent, especially in a hydrocarbon (such as those set forth above, for example) or an ether (such as those set forth above, for example), or an alcohol, e.g.,
• the organic solvent is miscible with water, e.g., lower alkanols are especially suitable.
• water e.g., lower alkanols are especially suitable.
• hydrogen sulfide added to the 2-methyl-4-isopropylidene-2-oxazolin-5-one which is now present as the salt.
• the oxazoline ring is split and the N-acetyl-DL-penicillamine thus formed is separated off by acidification.
• a preferred method for the recovery of the N-acetyl-DL-penicillamine is to add the mixture of 2-methyl-4-isopropylidine-2-oxazolin-5-one and chloroacetic acid dropwise into an at least stoichiometrical amount of the tertiary organic base in a lower alkanol. Hydrogen sulfide is led into this mixture at a temperature of about 40° to 60°C., the reaction mixture, in a given case after drawing off the alcohol, diluted with water, heated to a temperature between about 50° and 100°C. and finally by acidification regulate to a pH value which corresponds to that of the N-acetyl-DL-penicillamine or is less, and thereby to separate the N-acetyl-DL-penicillamine.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Applications Claiming Priority (2)

Publications (1)

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ID=5892266

Family Applications (1)

Country Status (9)

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Citations (1)

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• 1973
  • 1973-09-12 DE DE2345835A patent/DE2345835C2/de not_active Expired
• 1974
  • 1974-07-10 NL NL7409339A patent/NL7409339A/xx not_active Application Discontinuation
  • 1974-08-19 GB GB3636674A patent/GB1476989A/en not_active Expired
  • 1974-08-27 FR FR7429276A patent/FR2243188B1/fr not_active Expired
  • 1974-09-09 JP JP10376974A patent/JPS565226B2/ja not_active Expired
  • 1974-09-10 CA CA208,852A patent/CA1028353A/fr not_active Expired
  • 1974-09-10 BE BE6044741A patent/BE819760A/fr not_active IP Right Cessation
  • 1974-09-11 CH CH1236474A patent/CH596161A5/xx not_active IP Right Cessation
  • 1974-09-12 US US05/505,607 patent/US3956304A/en not_active Expired - Lifetime

Patent Citations (1)

Non-Patent Citations (1)

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